Pretreatment detection of circulating and tissue CD133(+) CD44(+) cancer stem cells as a prognostic factor affecting the outcomes in Egyptian patients with colorectal cancer

BACKGROUND AND AIM: Colorectal cancer is one of the most common malignant tumors worldwide. As CD133 and CD44 are notable markers of cancer stem cells (CSCs) identity, it is thought to be a predictive indicator for colorectal cancer. The aim of this study was to investigate the cell cycle state of CD133(+) CD44(+) and CD133(−) CD44(−)cells, isolated from primary human colorectal tumors, and to assess the clinical impact of CD133(+) CD44(+) CSCs on patients’ outcome regarding disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: Tissue samples were collected from 50 primary colorectal cancer patients. Flow cytometric analysis was performed to isolate tissue CD133(+) CD44(+) CSCs and CD133(−) CD44(−) tumor cells from primary colorectal cancer tissue to compare the cell cycle of both types of cells. Also circulating CSCs were assessed by flow cytometry. RESULTS: Higher percentage of tissue CD133(+) CD44(+) CSCs isolated from colorectal cancer patients was found in G0/G1 phase. However, tissue CD133(−) CD44(−) tumor cells were predominantly found in the S phase; there were significant negative correlations between tissue CD133(+) CD44(+) CSCs and DFS and OS (r=−0.470, P<0.001, respectively and r=−0.487, P<0.001, respectively), also significant negative correlations between tissue CSCs and DFS and OS (r=−0.548, P<0.001, respectively and r=−0.497, P<0.001, respectively). Only the pathological grade (P<0.004) and T stage (P<0.004) had a significant effect on circulating CSC counts. CONCLUSION: Tissue CD133(+) CD44(+) CSCs were more quiescent than tissue CD133(−) CD44(−) tumor cells and both circulating CSCs and tissue CSCs were considered independent negative prognostic factors on OS and DFS.